scholarly journals VD Versus VTD Induction: Similar Efficacy in Controlling Disease in Transplant Eligible Multiple Myeloma Patients Outside Clinical Trials

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5711-5711
Author(s):  
Federica Cocito ◽  
Silvia Mangiacavalli ◽  
Virginia Valeria Ferretti ◽  
Claudio Salvatore Cartia ◽  
Maya Ganzetti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Control ◽  
Real Life ◽  
Standard Of Care ◽  
Similar Efficacy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Overall Response ◽  
Free Rate

Abstract Autologous stem cell transplant (ASCT) remains the standard of care for Multiple Myeloma (MM) patients younger than 70 years old. The role of induction therapy is crucial within a program of high-dose therapy since deeper is the response before, higher is the outcome of transplant. In this study, we analyzed a real life setting of patients treated with three different induction approaches: VAD (Vincristine-Adriamycin-Dexamethasone), VD (Bortezomib - Dexamethasone), and VTD (Bortezomib-Thalidomide-Dexamethasone) in terms of depth of response, 2 years therapy-free rate and toxicity. One hundred and sixty-three MM patients (pts) were included in the analysis: 62 pts treated with VAD (38%), 44 with VD (27%) and 57 with VTD (35%). In VTD group 49 pts (86%) received Bortezomib subcutaneously. As shown in Table 1, patients of the three groups were similar for D&S stage (p 0.59), a higher rate of ISS stage 3 was observed in VAD group (p=0.019), patients in VTD group were significantly older (p=0.024), median follow-up was significantly lower in VTD pts (p<0.001). The overall response rates after induction were similar in all three groups (p=0.156), with higher rate of responses of good quality (CR+VGPR) for patients treated with Bortezomib-based combinations: VAD 24.2%, VD 52.3%, VTD 63.2% (p<0.001). No difference was observed between VTD and VD (p=0.258). A different pattern of responses was observed after transplant, VTD, in fact, was superior to VAD (p<0.001) and VD (p=0.012), while no difference was highlighted between VAD and VD (p=0.352). As a matter of fact, 2 years therapy-free rate were: 48% for patients treated with VAD vs 73% with VD vs 74% with VTD (p=0.189). Of note, however, bortezomib base therapy maintained its superiority with respect to VAD (p=0.03). No differences were observed between VD and VTD regimens in terms of toxicity of any grade and type (52.3% VD vs 52.6% VTD, p> 0.9), and of discontinuation rate (14% in VTD and 18% in VD, p=0.395). The incidence of all grades peripheral neuropathy (PN) was similar between VD and VTD (28.2% and 31.4% p=0.835), but grade 3-4 PN was significantly higher in VD group (no patients in VTD vs 18% in VD pts, p=0.078), probably due to different way of Bortezomib administration in VTD group (86% of pts received subcutaneous Bortezomib). In this study, we confirm that Bortezomib-based regimens are better than VAD in terms of overall response rate, good quality responses and long-term disease control. VTD is superior to VD in terms of good quality responses after transplant but disease control at 2 years is similar. Disclosures Corso: Janssen-Cilag: Honoraria.

Impact of High Dose Cyclophosphamide on the Outcome of Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4127-4127 ◽  
Author(s):  
Wendi A. Bacon ◽  
Gwynn D. Long ◽  
David A. Rizzieri ◽  
Mitchell E. Horwitz ◽  
John P. Chute ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Retrospective Analysis ◽  
Stem Cell Transplant ◽  
Standard Of Care ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Cell Mobilization

Abstract Abstract 4127 In the age of novel targeted agents, autologous stem cell transplant (ASCT) remains the standard of care for younger patients with newly diagnosed multiple myeloma (MM), offering similar treatment responses and overall survivals as standard chemotherapeutic agents but with the added benefit of a prolonged treatment-free period. Nevertheless, a standard of care for stem cell mobilization for ASCT has yet to be determined. Even in the era of new mobilization agents such as Plerixafor, Cyclophosphamide (Cy) and G-CSF combination remains the preferred mobilizing approach for patients with MM. Several studies have shown that Cy improves the stem cell yield at the expense of increased toxicity, but whether the administration of this chemotherapeutic agent pre-transplant has any impact on the long-term event-free and/or overall survival of myeloma patients remains controversial. In this study, we present a retrospective analysis of 186 patients with newly diagnosed MM who underwent ASCT with high-dose melphalan 200 mg/m2 (HDM) between December of 2000 and 2008 at our Institution. Eighty-three patients were mobilized with single agent G-CSF and 103 patients received high dose Cy (4 gm/m2) and G-CSF combination. Patient characteristics were similar between the treatment groups, including: age, gender, disease stage, and disease status prior to transplant. However, toxicity post-mobilization with Cy/G-CSF was significantly higher compared with G-SCF alone, including: febrile neutropenia (23%), hemorrhagic cystitis (8%), GI toxicity (57%), re-hospitalization due to complications and transplant delay (14%). The overall post-transplant toxicity was similar in the 2 groups, though the treatment related mortality was slightly higher in the Cy/G-CSF arm (4% versus 2%). Post transplant responses were not significantly different in the 2 groups, with 60% of patients achieving a VGPR or better after ASCT in the G-CSF group and 49% in the Cy/G-CSF group (p = 0.33). The median event-free survivals (EFS) for the Cy/G-CSF and G-CSF cohorts were 21.6 and 22.6 months, respectively, (p = 0.62) yielding no significant difference (Figure 1). Similarly, with a median follow up for surviving patients of 34.3 and 32.7 months, the median overall survivals were 68.2 and 62.3 months (p = 0.23) for the Cy/G-CSF and G-CSF cohorts, respectively (Figure 2). This retrospective analysis confirms that the addition of high dose Cy as part of the mobilizing regimen offers no improvement on the transplant outcome for patients with newly diagnosed myeloma and should therefore only be used in cases of difficult stem cell mobilization. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Daratumumab, Pomalidomide, and Dexamethasone (DPd) for the Treatment of Relapsed/Refractory Multiple Myeloma: A Single Institution Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5642-5642 ◽  
Author(s):  
Al-Ola Abdallah ◽  
Neil Dunavin ◽  
Brian McClune ◽  
Leyla Shune ◽  
Ajoy L. Dias ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitor ◽  
Research Funding ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Duration Of Treatment ◽  
Effective Treatment Option ◽  
Refractory Multiple Myeloma ◽  
Overall Response

Abstract Background: Daratumumab triplet regimens containing dexamethasone and lenalidomide or bortezomib are an effective treatment option for patients with relapsed/refractory multiple myeloma (RRMM). Daratumumab was recently FDA-approved in combination with the second-generation immunomodulatory drug, pomalidomide, and dexamethasone based (DPd) on results of the EQUULEUS study where overall response rates (ORR) of 60% were seen. The goal of this retrospective study was to analyze clinical outcomes of the DPd triplet regimen in either a daratumumab and pomalidomide naïve or refractory population of heavily pretreated RRMM patients at our institution. Methods: Thirty-two patients with RRMM treated with DPd at the University of Kansas Health System between November 2015 and July 2018 were included in our analysis. DPd consisted of 28-day cycles of daratumumab 16 mg/kg intravenously (weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, and every 4 weeks thereafter until disease progression); pomalidomide 4 mg orally (PO)on Days 1-21 and adjusted for cytopenia or toxicities; and dexamethasone 40 mg PO weekly adjusted based on tolerance. based on age. Responses were evaluated using IMWG criteria. Patient characteristics, disease course, and outcomes were summarized with descriptive statistics. Kaplan-Meier analyses were used to estimate progression-free (PFS) and overall survival (OS). Results:The median age was 64 years (range 44-83). Twenty-three patients (72%) had IgG isotype, 11 patients (34 %) had ISS stage III disease at diagnosis, 13 patients (41%) had high risk cytogenetics, and 13 patients (41%) had extramedullary disease. Median number of previous lines of therapy was 4 (1-9). Twenty-two patients (69%) received ≥3 prior therapies. Twenty-three patients (72%) were proteasome inhibitor refractory, 28 patients (88%) were immunomodulator refractory, 9 patients (28%) were daratumumab refractory, and 3 patients (15%) were double refractory to daratumumab and pomalidomide. Twenty-eight patients (88%) had received autologous stem cell transplant (ASCT) prior to DPd; 12 patients (38%) had ≥2 prior transplants. Median number of DPd cycles received was 6 (2-30) and the median duration of treatment was 5 months (2-30). At a median follow-up of 8.4 months (range: 2-29), the overall response rate (ORR) for all patients was 72% which compares favorably to the ORR of 60% in the EQUULEUS study. However, about half of the responses were partial responses (PR) (47%). The ORR rate for those who were refractory to either pomalidomide or daratumumab was 65%. The PFS was 8.3 months, while the median OS was not reached. Conclusion: DPd was recently approved for the treatment of RRMM. Our ORR compares favorably to the EQUULEUS study, however about half of responses were partial responses or better. Surprisingly, our analysis shows an impressive ORR in patients with previous exposure to proteasome inhibitor and immunomodulatory therapies in RRMM population, suggesting a benefit of DPd even in patients who received prior pomalidomide or daratumumab. Disclosures McGuirk: Astellas Pharma: Research Funding; Gamida Cell: Research Funding; Novartis Pharmaceuticals Corporation: Honoraria, Other: speaker, Research Funding; Pluristem Ltd: Research Funding; Kite Pharma: Honoraria, Other: travel accommodations, expenses, speaker ; Fresenius Biotech: Research Funding; Bellicum Pharmaceuticals: Research Funding. Ganguly:Daiichi Sankyo: Research Funding; Janssen: Consultancy; Amgen: Consultancy; Seattle Genetics: Speakers Bureau.

Efficacy of Novel Agents in Multiple Myeloma in Comparison to Autologous Stem Cell Transplant: A Retrospective Study in a Single Inner City Institution

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5118-5118
Author(s):  
Tareq Braik ◽  
Dayra Avila ◽  
Shivi Jain ◽  
Manila Gaddh ◽  
Barabara Yim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Median Survival ◽  
Standard Of Care ◽  
High Dose Chemotherapy ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Conventional Chemotherapy ◽  
Novel Therapy

Abstract Abstract 5118 Introduction: Since the mid 1990s, high dose chemotherapy with hematopoietic stem cell rescue has been considered the standard of care for front-line treatment in younger patients with multiple myeloma. This standard of care has been based on randomized controlled trials that compared autologus stem cell transplant (ASCT) with conventional chemotherapy. During the past decade, novel agents (NA), thalidomide, bortezomib and lenalinomide, have replaced conventional chemotherapy in the treatment of myeloma. These agents, used frontline, have shown promise in improving the outcome of myeloma patients without increasing toxicity. There are no studies to date comparing NA therapy to ASCT to determine whether there is a survival difference or whether NA therapy may reduce the need for transplantation. Many of our patients have no health insurance coverage and transplant is not a therapeutic option for them. We have attempted to compare the outcome of such patients receiving NA therapy with those in the literature who received conventional chemotherapy followed by ASCT. Methods: Ninety nine patients with multiple myeloma were treated at John H Stroger Hospital of Cook County between 2001 and 2011. All patients received novel agents (thalidomide, bortezomib and lenalinomide) as part of their therapy. Only 18/99 (18.2%) went for high-dose chemotherapy with ASCT and the remaining 81/99 (81.8%) received novel therapy without ASCT. We compared the outcome of patients who received novel therapy alone to a historical control group from the literature who received ASCT with conventional therapy (N Engl J Med 2003;348:1875–83). Overall survival was determined by Kaplan-Meier estimates. Results: We evaluated 99 consecutive myeloma patients (38% males and 61% female) of which 65% were African Americans, 19% Hispanics and 7% whites. All 3 stages (international staging system) of myeloma were equally represented. The median age at diagnosis was 60 years (40–85yr). Median follow up was 48 months (12–120). During the ten year follow up period, 60 patients (60.4%) have died. Twenty four out of 99 patients (24.2%) received only one line of therapy. 75 patients received more than one line of therapy. 75% received thalidomide-based therapy, 13% received bortezomib-based therapy and 12% received lenalinomide-based therapy. The median survival of patients who received novel therapy without ASCT (n=81) was 60 months, which is higher than the median survival of the historical controls who received ASCT reported by Child et al, N Engl J Med 2003;348:1875–83, (median survival = 54.1 months), the difference was statistically significant (P=0.0329). There was no statistically significant difference between the two groups by sex (p=0.927) and race (p=0.421). The 5-year survival of patients who received novel therapy without ASCT (n=81) was 48.2%. For those who were younger than 65 years (n=54), the median survival was 72 months and the 5-year survival was 58.1% in comparison to those who were 65 years and older (n=27), the median survival was 46 months and the 5-year survival was 29.2% (P=0.029). Conclusion: Novel agents are effective frontline therapy for multiple myeloma, especially in patients younger than 65. Our cohort had remarkable results in comparison to a historical population of patients who had ASCT with conventional chemotherapy. Since there is no curative therapy to date, a prospective randomized trial comparing NA with ASCT will be essential to clarify the role of ASCT in the era of novel therapy. Disclosures: No relevant conflicts of interest to declare.

Bortezomib, lenalidomide, and dexamethasone (VRD) is superior to lenalidomide, adriamycin, and dexamethasone (RAD) prior to risk-adapted transplant in newly diagnosed myeloma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8521-8521
Author(s):  
Stefan Knop ◽  
Christian Langer ◽  
Monika Martha Engelhardt ◽  
Florian Bassermann ◽  
Martin Schreder ◽  
...  
Keyword(s):  
Study Drug ◽  
Standard Of Care ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Phase 2 Study ◽  
Set Up ◽  
The Cost

8521 Background: High-dose chemotherapy (HDT) followed by autologous stem cell transplant (SCT) remains a standard of care in patients (pts) with newly diagnosed (ND) multiple myeloma (MM). While lenalidomide (R) maintenance is acknowledged to improve outcomes, intensified consolidation (such as tandem-SCT) has yielded conflicting results. Allogeneic (allo) SCT holds the promise of curative potential at the cost of higher treatment-related mortality (TRM). In a previous phase 2 study, we showed a very low TRM rate (6.1%) and feasibility of 12 months (mos) of R maintenance (maint), with auto/allo SCT after R/adriamycin/dexamethasone (RAD). This prompted us to compare, on a randomized rather than a “biological assignment” basis, a second auto- versus (vs) an allo-SCT in pts with an unfavorable prognosis. Methods: The current protocol (DSMM XIV, NCT01685814) was set up according to a double 2x2-factorial design. Post-induction (PInd) CR rate was the efficacy endpoint for the comparison of RAD vs bortezomib (V)/RD (VRD; 3 cycles each). If pts had achieved >VGPR to HDT, a second randomization (2ndR) compared immediate R maint (arm A2) with a second auto-SCT (B2). In case of < VGPR, pts were randomized between a second auto- (C2) and allo-SCT (D2). Planned R maint. duration was 36 mos, except after allo (12 mos). Results: Between 05/2012-06/2016, 476 pts were randomized and 469 received at least one dose of study drug. Pts’ median age was 55 (range, 32–65) years. 11.3% of pts had FISH del17p; 11.6% had t(4;14); and 4.4% had t(14;16). PInd CR rate was 11.8% (90% CI, 7.9%-16.3%) with RAD and 13.0% (90% CI, 8.9-18.0) with VRD (P = .697). 382 pts underwent R2 with 279 pts. (73%) in >VGPR and 103 (27%) in < VGPR, respectively. Median duration of R maint (N = 298) was 21.2 mos for A2, 23.1 mos for B2, 27.4 mos for C2, and 11.0 mos. for D2. At a median follow-up of 40.2 (0.5-87.0) months, median PFS from first randomization with RAD was 41.7 (95% CI, 35.4-48.5) mos vs. 53.7 (95% CI, 46.2-63.1) mos with VRD (P = .0439). Median PFS from 2ndR was 38.7 (95% CI, 30.3-47.3) mos for the 181 RAD vs. 50.7 (95% CI, 44.4-64.9) mos for the 201 VRD pts (P = .0126). Median overall survival (OS) cannot be estimated. With 47 deceased RAD vs 36 VRD pts, HR was .671 (95% CI, .435-1.037; P = .0703). Conclusions: In this study, median PFS benefit was 12 mos in favor of VRD vs. RAD despite comparable PInd CR. We show for the first time a len-PI to be superior to a len-chemo triplet, confirmed with positive OS trends. 3-year PFS for all consolidation arms will be presented. Clinical trial information: NCT01685814 .

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